1.Clinical and Immunological Responses in Ocular Demodecosis.
Jae Hoon KIM ; Yeoun Sook CHUN ; Jae Chan KIM
Journal of Korean Medical Science 2011;26(9):1231-1237
The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1beta, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1beta in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1beta and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders.
Acari/drug effects/physiology
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Adolescent
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Adult
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Aged
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Animals
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Blepharitis/drug therapy/*immunology/parasitology
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Chemokine CCL4/analysis
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Female
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Granulocyte Colony-Stimulating Factor/analysis
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Humans
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Interleukin-12/analysis
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Interleukin-13/analysis
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Interleukin-17/analysis
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Interleukin-1beta/analysis
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Interleukin-5/analysis
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Interleukin-7/analysis
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Male
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Middle Aged
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Tea Tree Oil/therapeutic use
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Tears/metabolism
2.Animal study for airway inflammation triggered by gastroesophageal reflux.
Yun-gang LAI ; Zhong-gao WANG ; Feng JI ; Ji-min WU ; Xiu CHEN ; Zhen LI ; Shu-kui DONG
Chinese Medical Journal 2009;122(22):2775-2778
BACKGROUNDGastroesophageal reflux disease with extra-esophageal symptoms, especially those with respiratory distress was attracting more and more attention. The related mechanisms were still in controversy. The purpose of the work was to explore airway inflammation triggered by gastroesophageal reflux.
METHODSSixteen Sprague-Dawley rats were used as study group and 9 as control. In the study group, a plastic extender with a trumpet-shaped distal end was inserted into the lower esophagus to dilate the cardia, the pylorus was ligated. One ml of 0.1 mol/L hydrochloric acid was injected into the stomach. While a simple laparotomy was performed for control animals. All animals from two groups were sacrificed 24 hours after operation. Then tracheotomy was carried and the bronchoalveolar lavage fluid was collected in all animals. Cells in the fluid were counted and levels of interleukin (IL)-5, -6, -8 in it were measured.
RESULTSCompared with control group, the study group presented a neutrophil pattern of airway inflammation and an elevated concentration of IL-5, -6, -8 with no significant difference regarding eosinophil count.
CONCLUSIONThe gastroesophageal reflux-triggered airway inflammation is characterized by a neutrophilic airway inflammation which differed from that caused by asthma, and enhanced levels of IL-5, -6 and -8, which are similar to that caused by asthma.
Animals ; Asthma ; etiology ; Bronchoalveolar Lavage Fluid ; immunology ; Disease Models, Animal ; Female ; Gastroesophageal Reflux ; complications ; Inflammation ; etiology ; Interleukin-5 ; analysis ; Interleukin-6 ; analysis ; Interleukin-8 ; analysis ; Male ; Rats ; Rats, Sprague-Dawley
3.Expression of SDF-1 in lung tissues and intervention of AMD3100 in asthmatic rats.
Li-Ping ZOU ; Li-Xia WANG ; Yan ZHANG ; Wen-Li DU
Chinese Journal of Contemporary Pediatrics 2011;13(4):321-325
OBJECTIVETo study the expression of stromal cell derived factor-1(SDF-1) in the airway and to investigate the role of SDF-1 receptor antagonist AMD3100 intervention in rats with asthma.
METHODSThirty Sprague-Dawley rats were randomly divided into three groups: normal control and asthma with and without AMD3100 intervention. The rat model of asthma was prepared by aerosolized ovalbum (OVA) challenge. The AMD3100 intervention group was administered with AMD3100 of 50 μg 30 minutes before challenge every other day, for 10 times. The characteristic airway inflammation and alterations of airway structures were observed by hemetoxylin and eosin staining. The levels of interleukin 4 and interleukin 5 in whole lung homogenates were measured using ELISA. RT-PCR was used to evaluate the expression of SDF-1 mRNA in the lung.
RESULTSThe airway wall thickness in the untreated asthma group was greater than that in the control and the AMD3100 intervention groups (P<0.05). The levels of interleukin 4 and interleukin 5 in whole lung homogenates in the AMD3100 intervention group were lower than those in the untreated asthma group (P<0.05). The expression of SDF-1 mRNA in the untreated asthma group was higher than that in the control and the AMD3100 intervention groups (P<0.05).
CONCLUSIONSSDF-1 may be associated with airway inflammation and remodeling in rats with asthma. AMD3100 may reduce the airway inflammation and improve airway remodeling by inhibiting the bioactivity of SDF-1.
Animals ; Asthma ; drug therapy ; etiology ; metabolism ; Chemokine CXCL12 ; analysis ; antagonists & inhibitors ; genetics ; physiology ; Female ; Heterocyclic Compounds ; pharmacology ; Interleukin-4 ; analysis ; Interleukin-5 ; analysis ; Lung ; metabolism ; pathology ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptors, CXCR4 ; antagonists & inhibitors
4.Relationship Between Sputum Inflammatory Markers and Osmotic Airway Hyperresponsiveness During Induction of Sputum in Asthmatic Patients.
Journal of Korean Medical Science 2001;16(4):411-416
Hypertonic saline aerosols are being used increasingly for bronchial provocation testing and induction of sputum. The aims of this study were to assess the response to challenge with 3% hypertonic saline administered via a ultrasonic nebulizer in patients with asthma, and to evaluate relationship between % fall of FEV1 during induction of sputum (osmotic airway hyperresponsiveness; osmotic AHR) and biochemical markers of induced sputum. We investigated changes in FEV1 in response to inhaling ultrasonically nebulized 3% saline in 25 patients with asthma and 10 control subjects. FEV1 was measured before, during, and after induction of sputum. We used fluoroimmunoassay to detect eosinophil cationic protein (ECP), immunohistochemical staining to detect EG2+ (secretory form of ECP) eosinophils, and a sandwich ELISA to detect interleukin (IL)-5. Protein concentration was determined by using bicinchoninic acid protein assay reagent. Asthmatics, compared with controls, had significantly higher osmotic AHR. Moderate to severe asthmatics had significantly higher osmotic AHR compared to mild asthmatics. Osmotic AHR was significantly correlated with the proportion of eosinophils, the levels of ECP, EG2+ eosinophils, IL-5, and proteins. These data suggest that osmotic AHR is closely related to the clinical status and biochemical markers of sputum supernatant in asthmatic patients.
Adult
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Asthma/*physiopathology
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Biological Markers
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Blood Proteins/analysis
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Bronchial Hyperreactivity/*etiology
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Female
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Forced Expiratory Volume
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Human
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Interleukin-5/analysis
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Male
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Middle Age
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Osmotic Pressure
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Sputum/*chemistry
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Vital Capacity
5.Effect of early allergen immunization on the development of allergic rhinitis in mouse.
Yue ZHOU ; Jian-jun CHEN ; Zhong-yuan LU ; Wei-jia KONG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2010;45(1):52-55
OBJECTIVETo investigate the effect of early allergen exposure on later development of allergic rhinitis in mouse.
METHODSTwenty-four BALB/c neonates were randomly divided into 4 groups (low-dose group, high-dose group, negative control group and positive control group), each group had 6 mice. The mice were administered ovalbumin (OVA) by subcutaneous injection on day 1, 5, 12 after birth (10 μg OVA in 0.05 ml saline for low-dose group, 1000 μg OVA in 0.05 ml saline for high-dose group, only saline for negative and positive control group). Then the mice were sensitized and intranasally challenged with OVA (saline without OVA was used in negative control group) after 6 weeks. Symptoms, histopathological changes of nasal mucosa were observed, OVA-IgE in serum was examined, cytokines IL-4, IL-5 and IFN-gamma were detected in the supernatant of cultured splenic mononuclear cells.
RESULTSCompared to the positive control group, symptoms and nasal mucosa histological changes of high-dose group was indistinctive. The level of OVA-IgE and cytokines IL-4, IL-5 (x(-) +/- s) in high-dose group [(265.11 +/- 26.29), (446.39 +/- 72.83) and (171.24 +/- 15.66) pg/ml, respectively] were significantly lower than those in positive control group [(665.85 +/- 43.15), (1113.45 +/- 30.47), (255.36 +/- 30.96) pg/ml, respectively, t value were 0.000, 0.000 and 0.009, respectively, all P < 0.05]. The level of IFN-γ in high-dose group [(319.74 +/- 56.30) pg/ml] was significantly higher than those in positive control group [(170.02 +/- 14.50) pg/ml, t = 0.000, P < 0.05]. There was no significant difference of the results between the low-dose group and positive control group.
CONCLUSIONSNeonatal immunization with high-dose OVA inhibited the future allergic rhinitis symptoms, nasal histological changes, serum OVA-IgE levels and Th1/Th2 cytokine imbalance, resulting in the protective effect.
Allergens ; immunology ; Animals ; Animals, Newborn ; Dose-Response Relationship, Immunologic ; Immunoglobulin E ; blood ; Interferon-gamma ; analysis ; Interleukin-4 ; analysis ; Interleukin-5 ; analysis ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; immunology ; Nasal Provocation Tests ; Ovalbumin ; immunology ; Rhinitis, Allergic, Perennial ; immunology ; prevention & control
6.Identification of UVB Effects on Gene Expressed by Normal Human Melanocytes.
Hyoung Seob KIM ; Hyun Ho PARK ; Mu Hyoung LEE
Korean Journal of Dermatology 2003;41(12):1597-1602
BACKGROUND: Irradiation of the skin with ultraviolet rays result in alterations of immune response as well as melanogenesis and melanocarcinogenensis. These effects are largely mediated by soluble mediators released from epidermal cells in response to ultraviolet rays. OBJECTIVE: To evaluate the effect of ultraviolet B (UVB) irradiation on the normal human melanocyte gene expression. METHODS: We demonstrated genes modulated by UVB irradiation among over 300 genes coding CDs, cytokins, growth factors, and growth factor receptors in normal human melanocytes by cDNA microarray technique. RESULTS: Two genes out of 384 genes in cultured normal human melanocytes were found up-regulated following UVB irradiation. They are the genes coding lactotransferrin and CD160. Forty one genes out of 384 genes were found down-regulated by UVB irradiation. They included the genes coding IL-9, IL-5, TNF-alpha, TNF-beta, IL-6 receptor and CD20. CONCLUSION: These results provide the basis for future studies on the immunologic role in modulated genes by UV-stressed human melanocytes.
Clinical Coding
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Gene Expression
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Humans*
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Intercellular Signaling Peptides and Proteins
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Interleukin-5
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Interleukin-9
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Lactoferrin
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Lymphotoxin-alpha
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Melanocytes*
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Oligonucleotide Array Sequence Analysis
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Receptors, Growth Factor
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Receptors, Interleukin-6
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Skin
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Tumor Necrosis Factor-alpha
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Ultraviolet Rays
7.Comparison Between Signature Cytokines of Nasal Tissues in Subtypes of Chronic Rhinosinusitis
Dong Kyu KIM ; Kyoung Mi EUN ; Min Kyung KIM ; Deuktae CHO ; Sun A HAN ; Sang Yoon HAN ; Yuju SEO ; Dong Han LEE ; Seong Ho CHO ; Dae Woo KIM
Allergy, Asthma & Immunology Research 2019;11(2):201-211
PURPOSE: Endotype in chronic rhinosinusitis (CRS) has been established in the last decade. However, the exact immunologic profile of CRS still has controversy because it has a considerable immunologic heterogeneity. Therefore, we investigated various inflammatory mediators according to different nasal tissues in chronic rhinosinusitis and compared them within the same subject. METHODS: We collected uncinate process mucosa (UP) and nasal polyp (NP) tissues from controls, CRS without NP (CRSsNP) and CRS with NP (CRSwNP). Expression levels of 28 inflammatory mediators including T helper (Th) 1, Th2, Th17, proinflammatory cytokines and remodeling markers were determined by multiplex immunoassay and were analyzed using paired tests as well as principal component analysis (PCA) to investigate endotype in each subtype of CRS. RESULTS: Signature inflammatory mediators are interleukin (IL)-5, C-C motif chemokine ligand (CCL)-24, monocyte chemoattractant protein (MCP)-4, and vascular cell adhesion molecule (VCAM)-1 in eosinophilic NP, whereas IL-17A, IL-1β, and matrix metallopeptidase (MMP)-9 were detected as signature inflammatory markers in non-eosinophilic NP. Despite differences in inflammatory cytokine profile between eosinophilic and non-eosinophilic NP, the common upregulation of IL-5, CCL-11, IL-23, IL-2Rα, VCAM-1, MMP-3 and MMP-9 were shown in NP compared to UP within the same subject. In the PCA, we observed that Th2 immune response was helpful in discriminating between nasal tissues in subtypes of CRS and that there was a partial overlap between non-eosinophilic NP and eosinophilic NP in terms of Th2 mediators. CONCLUSIONS: Commonly upregulated mediators in NP were Th2-associated, compared with UP regardless of CRS subtypes, whereas signature markers were distinct in each NP subtype. These findings imply that Th2 inflammatory responses may play a role in the development of NP regardless of CRSwNP subtypes.
Cytokines
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Eosinophils
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Immunoassay
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Interleukin-17
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Interleukin-23
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Interleukin-5
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Interleukins
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Monocytes
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Mucous Membrane
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Nasal Polyps
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Passive Cutaneous Anaphylaxis
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Population Characteristics
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Principal Component Analysis
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Rhinitis
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Sinusitis
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Up-Regulation
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Vascular Cell Adhesion Molecule-1
8.Relationship of Microbial Profile With Airway Immune Response in Eosinophilic or Neutrophilic Inflammation of Asthmatics
Ji Hye SON ; Jung Hyun KIM ; Hun Soo CHANG ; Jong Sook PARK ; Choon Sik PARK
Allergy, Asthma & Immunology Research 2020;12(3):412-429
PURPOSE: Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.METHODS: Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.RESULTS: The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).CONCLUSIONS: Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.
Asthma
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Colony-Stimulating Factors
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Cytokines
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Enzyme-Linked Immunosorbent Assay
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Eosinophils
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Haemophilus parainfluenzae
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Inflammasomes
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Inflammation
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Interleukin-13
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Interleukin-33
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Interleukin-5
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Microbiota
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Necrosis
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Neisseria
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Neutrophils
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Phenotype
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Pneumonia
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Porphyromonas
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Sequence Analysis
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Sputum
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Streptococcus
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Streptococcus pneumoniae
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Veillonella
9.IL-4 and IL-5 Secretions Predominate in the Airways of Wistar Rats Exposed to Toluene Diisocyanate Vapor.
Kouame KOUADIO ; Kui Cheng ZHENG ; Abdoulaye Abba TOURE ; Mireille DOSSO ; Hidemi TODORIKI
Journal of Preventive Medicine and Public Health 2014;47(1):57-63
OBJECTIVES: We established a Wistar rat model of asthma caused by toluene diisocyanate (TDI) exposure, and investigated the relationship between TDI exposure concentrations and respiratory hypersensitivity, airway inflammation, and cytokine secretions in animals, to better understand the mechanism of TDI induced occupational asthma. METHODS: Wistar rats were exposed to two different concentrations of TDI vapor four hours a day for five consecutive days. Bronchoalveolar lavage (BAL) was performed, and differential leucocytes from the BAL fluid were analyzed. Lung histopathological examination was carried out to investigate the inflammatory status in the airways. Production of cytokines interleukin (IL)-4 and IL-5 productions in the BAL fluid in vivo was determined with enzyme-linked immunosorbent assay kits. RESULTS: The TDI-exposed rats exhibited greater airway hypersensitivity symptoms than the control rats. The BAL differential cell count and lung histopathological examination demonstrated that inflammation reactions were present in both the central and peripheral airways, characterized with marked infiltration of eosinophils in the TDI-exposed rats. The cytokine assay showed that IL-4 and IL-5 were predominantly produced in the BAL fluid in vivo. CONCLUSIONS: These findings imply that TDI exposure concentrations may greatly affect the occurrence and extent of inflammatory events and that Th2 type cytokines may play an important role in the immunopathogenesis of TDI-induced occupational respiratory hypersensitivity.
Animals
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Bronchoalveolar Lavage Fluid/chemistry/cytology
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Enzyme-Linked Immunosorbent Assay
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Eosinophils/cytology/immunology
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Female
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Gases/chemistry
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Hypersensitivity/pathology
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Interleukin-4/*analysis
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Interleukin-5/*analysis
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Lung/*drug effects/pathology/secretion
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Rats
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Rats, Wistar
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Toluene 2,4-Diisocyanate/*toxicity
10.Relationship between bone marrow-derived CD34 + cells expressing interleukin-5 receptor messenger RNA and asthmatic airway inflammation.
Hui MAO ; Zeng-li WANG ; Fu-yu LI ; Chun-tao LIU ; Song LEI
Chinese Medical Journal 2004;117(1):24-29
BACKGROUNDAsthma is clinically related with the degree of eosinophilic inflammation. How asthmatic airway inflammation is affected is still poorly understood. So the effects of bone marrow-derived hematopoietic cells expressing CD(34) (CD(34)(+)) and interleukin-5 (IL-5) receptor messenger RNA (IL-5R mRNA+) on asthmatic airway inflammation were investigated.
METHODSBalb/c mice were sensitized and challenged by ovalbumin (OVA) to establish an asthmatic model while control mice were sensitized and exposed to sterile saline. The mice were killed at different time points after being challenged by OVA and sterile saline. Then, bronchoalveolar lavage fluid (BALF), peripheral blood (PB) and bone marrow (BM) were prepared. Eosinophils in PB (PBEOS) and BALF (BALFEOS), nuclear cells in BALF, PB and BM were counted. By flow cytometry, the percentage of CD(34)(+) cells to nucleated cells in PB, BM and the relative number of CD(34)(+) cells in PB (PBCD(34)(+)) and BM (BMCD(34)(+)) were calculated. Immunocytochemistry and in situ hybridization were used to investigate the hematopoietic cells with co-localized expression of CD(34) and IL-5R mRNA in BM (BMCD34+IL-5R mRNA+). The percentage of BMCD34+IL-5R mRNA+ to BMCD(34)(+) was calculated.
RESULTSTwelve hours after challenge by OVA, BALFEOS and PBEOS in the experimental group were significantly higher than those in the control group (P < 0.01). Twenty-four hours after OVA challenge, BALFEOS, PBEOS and BMCD34+IL-5R mRNA+ were elevated maximally, significantly different from those in the control group (P < 0.01). Forty-eight hours after OVA challenge, BALFEOS and BMCD34+IL-5R mRNA+ were still significantly higher than those of the controls (P < 0.01). The other markers reverted to normal. In 60 mice, BMCD34+IL-5R mRNA+ was closely correlated with the BALEOS, PBEOS, BMCD(34)(+) and BMCD(34)(+) (%) (P < 0.05).
CONCLUSIONSThe amount of CD(34)(+) cells expressing IL-5R mRNA increased in the BM of asthmatic model mice, which favors eosinophilopoiesis and eosinophilic airway inflammation. A signal pathway exists between the lungs and the bone marrow, which is involved in the initiation and maintenance of asthmatic airway inflammation.
Animals ; Antigens, CD34 ; analysis ; Asthma ; immunology ; Bone Marrow Cells ; cytology ; Bronchoalveolar Lavage Fluid ; cytology ; Inflammation ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; analysis ; Receptors, Interleukin ; genetics ; Receptors, Interleukin-5